Nearly half of patients with heart disease become non-adherent to their prescribed therapies within a year of treatment initiation. This is a central and modifiable reason why cardiovascular disease remains a leading cause of death in the US. Despite numerous attempts to develop interventions aimed at improving adherence, these attempts have had varying and often limited success; one explanation could be that underlying barriers to adherence are not being addressed. Those interventions that have been successful often make medications easier to take but are frequently expensive to implement or deployed too late. Developing a novel provider- facing intervention that modifies medication ?adherability?, defined as the properties of medications that make them difficult for patients to take, could be especially impactful and relatively inexpensive. For example, more than 30% of patients report difficulties swallowing prescribed medicines, yet little is known how this ?adherability? affects long-term adherence and clinical outcomes, and few interventions focus on these issues. To this end, Dr. Lauffenburger?s K01 proposal incorporates a novel prophylactic, patient-centric approach to provider behavior change for cardiovascular disease management. Providers often do not know what the medications they prescribe actually look like or what aspects of the medications are acceptable to or preferred by their patients. This study will uniquely incorporate patient perspectives about medication properties that lead to poor adherence in the design of a scalable provider-facing clinical decision support intervention. The proposed aims are to: (1) develop a comprehensive framework of cardiovascular medication properties, such as appearance, side-effect profiles, or dosing, that may lead to poor adherence using patient focus groups; (2) rigorously evaluate their effects on adherence and clinical outcomes in large national data sources; (3) develop and externally validate a novel clinical prediction rule for medication adherability; and (4) develop and pilot test novel web- and electronic health record-based prescribing tools based on the prediction rule for providers. The expected overall impact of this innovative proposal is that it will fundamentally advance how to personalize medications for patients to ultimately improve adherence and health outcomes. Dr. Lauffenburger has a unique background as a practicing pharmacist trained in epidemiology with a proven commitment to research. This proposal includes an educational plan that will address gaps in her training: expertise in behavioral sciences, prediction modeling, and implementation research. The mentorship team, led by Niteesh Choudhry, an expert in adherence and implementation, includes well-known experts in cardiovascular trials (Elliott Antman, co-mentor), biostatistics (Robert Glynn, co-mentor), and behavioral sciences (Daniel Solomon, co-mentor), and will ensure scientific success and training. By the conclusion of this program, she will be able to independently design, target, and evaluate behavioral interventions for heart diseases. The results of the proposed K01 will be invaluable pilot work for a planned R01-level application.